Flies have been used as a model system for the study of aging for nearly a century. Despite a large literature devoted to fly aging, very little has been published about the underlying pathologies that limit fly longevity. The overall goals of the present study are to define the pathology of aging flies at the level of light microscopy using standard histopathologic techniques. In preliminary studies of aging male flies of the Canton S strain we have found this approach to be fast, cheap and richly informative. We have identified a range of pathologic changes that parallel those seen in many vertebrates, including humans. We have made the novel observation of the age-dependent development of what appear to be intestinal epithelial neoplasms. Other pathologic changes we have observed include progressive atrophy of internal organs, the accumulation of age pigments, the development of intracellular inclusions, changes in the distribution and histologic appearance of adipose tissue and increased susceptibility to pathogens. Based on these preliminary observations we propose to further explore the pathology of aging flies. [unreadable] Specific Aim 1: Test the hypothesis that aging flies develop intestinal and/or other neoplasms. We will use standard techniques of histopathology to systematically search for tumors in the intestines and other organ systems of male and female Canton S flies sacrificed at defined ages throughout their life spans. Specimens will also be analyzed for the presence of other pathologic changes including atrophy of internal organs, the development of intracellular inclusions, the formation of age pigments and infections. [unreadable] Specific Aim 2: Test the hypothesis that dietary restriction delays the onset and or severity of age-related pathology in the fly. Dietary restriction has been shown to increase the life spans of many organisms including mice, rats and flies. The mechanism of this effect in flies is unknown, although in mice and rats it has been shown to be mediated in part through the delay in onset of age-related pathologies. We will investigate the possibility that a similar mechanism is at work in flies. This will be the first study of the pathology of aging flies subjected to dietary restriction ever conducted. We believe the studies outlined here will substantially increase understanding of the aging fly. They will include the first systematic pathologic analyses of aging female flies. We anticipate that we will characterize new targets for the experimental modulation of the aging process in one of the world's best-studied and most tractable model organisms. [unreadable] [unreadable]